Skip to main content
SpringerLink
Log in

Predictors of respiratory decline in myotonic dystrophy type 1 (DM1): a longitudinal cohort study

  • Original article
  • Published:
Acta Neurologica Belgica Aims and scope Submit manuscript

Abstract

We studied 33 patients affected by juvenile and adult myotonic dystrophy type 1 (DM1). The aim of the study was to assess clinical and laboratory parameters that could predict the requirement of noninvasive ventilation (NIV) in DM1. Secondary outcome was to assess the interplay between genetic profile, muscle impairment severity and presence of cardiac comorbidities.Patients with genetic diagnosis of DM1 were recruited. An abnormal trinucleotide repeat (CTG) expansion of dystrophy protein kinase gene (DMPK) on chromosome 19q13.3 was the prerequisite for inclusion. The number of triplet repeats was measured in genomic DNA to classify subjects. A multidisciplinary team evaluated the patients every 6–8 months up to 18 years with serial cardiological and respiratory function assessments. Neurological progression was monitored using a validated DM1-specific rating scale (MIRS). Independent variables considered for the study outcomes were gender, genetic status, age of presentation, MIRS scores, and results of pulmonary function tests (PFTs).Patients were 17 males (51.5%) and 16 females (48.5%). 16 cases were younger than mean age of 31.4 years, the remaining 17 were up to 65. 12 subjects (36.4%) underwent NIV during follow up. Cardiac comorbidities were detected in 63.6% of cases and in 91% of patients in NIV. Among PFTs, forced vital capacity (FVC) was a reliable indicator of respiratory decline. FVC values were significantly associated with clinical muscle severity assessed by MIRS.Severity of muscular impairment, CTG expansion size, age and presence of cardiac comorbidities predict respiratory impairment in DM1

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bouchard J-P, Cossette L, Bassez G, Puymirat J (2015) Natural history of skeletal muscle involvement in myotonic dystrophy type 1: a retrospective study in 204 cases. J Neurol 262:285–293. https://doi.org/10.1007/s00415-014-7570-x

    Article  CAS  PubMed  Google Scholar 

  2. Boussaïd G, Wahbi K, Laforet P et al (2018) Genotype and other determinants of respiratory function in myotonic dystrophy type 1. Neuromuscul Disord 28:222–228. https://doi.org/10.1016/j.nmd.2017.12.011

    Article  PubMed  Google Scholar 

  3. Contardi S, Pizza F, Falzone F et al (2012) Development of a disability scale for myotonic dystrophy type 1: functional disability scale for DM1 patients. Acta Neurol Scand 125:431–438. https://doi.org/10.1111/j.1600-0404.2011.01587.x

    Article  CAS  PubMed  Google Scholar 

  4. Dogan C, De Antonio M, Hamroun D et al (2016) Gender as a modifying factor influencing myotonic dystrophy type 1 phenotype severity and mortality: a nationwide multiple databases cross-sectional observational study. PLoS ONE 11:e0148264. https://doi.org/10.1371/journal.pone.0148264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gagnon C, Chouinard MC, Laberge L et al (2010) Health supervision and anticipatory guidance in adult myotonic dystrophy type 1. Neuromuscul Disord 20:847–851. https://doi.org/10.1016/j.nmd.2010.08.006

    Article  CAS  PubMed  Google Scholar 

  6. Mahadevan M, Tsilfidis C, Sabourin L et al (1992) Myotonic dystrophy mutation: an unstable CTG repeat in the 3’ untranslated region of the gene. Science 255:1253–1255. https://doi.org/10.1126/science.1546325

    Article  CAS  PubMed  Google Scholar 

  7. Meola G (2013) Clinical aspects, molecular pathomechanisms and management of myotonic dystrophies. Acta Myol 32:154–165 (PMID: 24803843)

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Thornton CA (2014) Myotonic dystrophy. Neurol Clin 32:705–719. https://doi.org/10.1016/j.ncl.2014.04.011

    Article  PubMed  PubMed Central  Google Scholar 

  9. Gagnon C, Petitclerc É, Kierkegaard M et al (2018) A 9-year follow-up study of quantitative muscle strength changes in myotonic dystrophy type 1. J Neurol 265:1698–1705. https://doi.org/10.1007/s00415-018-8898-4

    Article  PubMed  Google Scholar 

  10. Mathieu J, Boivin H, Meunier D et al (2001) Assessment of a disease-specific muscular impairment rating scale in myotonic dystrophy. Neurology 56:336–340. https://doi.org/10.1212/WNL.56.3.336

    Article  CAS  PubMed  Google Scholar 

  11. Turner C, Hilton-Jones D (2014) Myotonic dystrophy: diagnosis, management and new therapies. Curr Opin Neurol 27:599–606. https://doi.org/10.1097/WCO.0000000000000128

    Article  PubMed  Google Scholar 

  12. Udd B, Krahe R (2012) The myotonic dystrophies: molecular, clinical, and therapeutic challenges. Lancet Neurol 11:891–905. https://doi.org/10.1016/S1474-4422(12)70204-1

    Article  CAS  PubMed  Google Scholar 

  13. Hammarén E, Kjellby-Wendt G, Lindberg C (2015) Muscle force, balance and falls in muscular impaired individuals with myotonic dystrophy type 1: a five-year prospective cohort study. Neuromuscul Disord 25:141–148. https://doi.org/10.1016/j.nmd.2014.11.004

    Article  PubMed  Google Scholar 

  14. Ashizawa T, Gagnon C, Groh WJ et al (2018) Consensus-based care recommendations for adults with myotonic dystrophy type 1. Neurol Clin Pract 8:507–520. https://doi.org/10.1212/CPJ.0000000000000531

    Article  PubMed  PubMed Central  Google Scholar 

  15. Petitclerc É, Hébert LJ, Mathieu J et al (2018) Relationships between lower limb muscle strength impairments and physical limitations in DM1. J Neuromuscul Dis 5:215–224. https://doi.org/10.3233/JND-170291

    Article  PubMed  Google Scholar 

  16. Wahbi K, Porcher R, Laforêt P et al (2018) Development and validation of a new scoring system to predict survival in patients with myotonic dystrophy type 1. JAMA Neurol 75:573. https://doi.org/10.1001/jamaneurol.2017.4778

    Article  PubMed  PubMed Central  Google Scholar 

  17. Boussaïd G, Lofaso F, Santos DB et al (2016) Factors influencing compliance with non-invasive ventilation at long-term in patients with myotonic dystrophy type 1: a prospective cohort. Neuromuscul Disord 26:666–674. https://doi.org/10.1016/j.nmd.2016.07.014

    Article  PubMed  Google Scholar 

  18. Naddaf E, Milone M (2017) Hereditary myopathies with early respiratory insufficiency in adults: respiratory failure myopathies. Muscle Nerve 56:881–886. https://doi.org/10.1002/mus.25602

    Article  PubMed  Google Scholar 

  19. Hermans MCE, Pinto YM, Merkies ISJ et al (2010) Hereditary muscular dystrophies and the heart. Neuromuscul Disord 20:479–492. https://doi.org/10.1016/j.nmd.2010.04.008

    Article  CAS  PubMed  Google Scholar 

  20. Pfeffer G, Povitz M, Gibson GJ, Chinnery PF (2015) Diagnosis of muscle diseases presenting with early respiratory failure. J Neurol 262:1101–1114. https://doi.org/10.1007/s00415-014-7526-1

    Article  PubMed  Google Scholar 

  21. Poussel M, Thil C, Kaminsky P et al (2015) Lack of correlation between the ventilatory response to CO2 and lung function impairment in myotonic dystrophy patients: Evidence for a dysregulation at central level. Neuromuscul Disord 25:403–408. https://doi.org/10.1016/j.nmd.2015.02.006

    Article  PubMed  Google Scholar 

  22. Shneerson JM, Simonds AK (2002) Noninvasive ventilation for chest wall and neuromuscular disorders. Eur Respir J 20:480–487. https://doi.org/10.1183/09031936.02.00404002

    Article  CAS  PubMed  Google Scholar 

  23. Thil C, Agrinier N, Chenuel B, Poussel M (2017) Longitudinal course of lung function in myotonic dystrophy type 1. Muscle Nerve 56:816–818. https://doi.org/10.1002/mus.25604

    Article  CAS  PubMed  Google Scholar 

  24. Sansone VA, Gagnon C (2015) 207th ENMC Workshop on chronic respiratory insufficiency in myotonic dystrophies: Management and implications for research, 27–29 June 2014, Naarden, The Netherlands. Neuromuscul Disord 25:432–442. https://doi.org/10.1016/j.nmd.2015.01.011

    Article  CAS  PubMed  Google Scholar 

  25. Hawkins AM, Hawkins CL, Abdul Razak K et al (2019) Respiratory dysfunction in myotonic dystrophy type 1: a systematic review. Neuromuscul Disord 29:198–212. https://doi.org/10.1016/j.nmd.2018.12.002

    Article  CAS  PubMed  Google Scholar 

  26. Monteiro R, Bento J, Gonçalves MR et al (2013) Genetics correlates with lung function and nocturnal ventilation in myotonic dystrophy. Sleep Breath 17:1087–1092. https://doi.org/10.1007/s11325-013-0807-6

    Article  PubMed  Google Scholar 

  27. Rossi S, Della Marca G, Ricci M et al (2019) Prevalence and predictor factors of respiratory impairment in a large cohort of patients with Myotonic Dystrophy type 1 (DM1): a retrospective, cross sectional study. J Neurol Sci 399:118–124. https://doi.org/10.1016/j.jns.2019.02.012

    Article  PubMed  Google Scholar 

  28. Vivekananda U, Turner C (2019) A model to predict ventilator requirement in myotonic dystrophy type 1. Muscle Nerve 59:683–687. https://doi.org/10.1002/mus.26471

    Article  PubMed  Google Scholar 

  29. Bogaard JM, van der Meché FG, Hendriks I, Verves C (1992) Pulmonary function and resting breathing pattern in myotonic dystrophy. Lung 170:143–153. https://doi.org/10.1007/bf00174317

    Article  CAS  PubMed  Google Scholar 

  30. Bégin P, Mathieu J, Almirall J, Grassino A (1997) Relationship between chronic hypercapnia and inspiratory-muscle weakness in myotonic dystrophy. Am J Respir Crit Care Med 156:133–139. https://doi.org/10.1164/ajrccm.156.1.9509041

    Article  PubMed  Google Scholar 

  31. Bucci E, Testa M, Licchelli L et al (2018) A 34-year longitudinal study on long-term cardiac outcomes in DM1 patients with normal ECG at baseline at an Italian clinical centre. J Neurol 265:885–895. https://doi.org/10.1007/s00415-018-8773-3

    Article  PubMed  Google Scholar 

  32. Chong-Nguyen C, Wahbi K, Algalarrondo V et al (2017) Association between mutation size and cardiac involvement in myotonic dystrophy type 1: an analysis of the DM1-heart registry. Circ Cardiovasc Gen 10(3):e001526. https://doi.org/10.1161/CIRCGENETICS.116.001526

    Article  CAS  Google Scholar 

  33. Lau JK, Sy RW, Corbett A, Kritharides L (2015) Myotonic dystrophy and the heart: a systematic review of evaluation and management. Int J Cardiol 184:600–608. https://doi.org/10.1016/j.ijcard.2015.03.069

    Article  CAS  PubMed  Google Scholar 

  34. Wahbi K, Babuty D, Probst V et al (2017) Incidence and predictors of sudden death, major conduction defects and sustained ventricular tachyarrhythmias in 1388 patients with myotonic dystrophy type 1. Eur Heart J 38:751–758. https://doi.org/10.1093/eurheartj/ehw569

    Article  PubMed  Google Scholar 

  35. Petri H, Vissing J, Witting N et al (2012) Cardiac manifestations of myotonic dystrophy type 1. Int J Cardiol 160:82–88. https://doi.org/10.1016/j.ijcard.2011.08.037

    Article  PubMed  Google Scholar 

  36. Lund M, Diaz LJ, Ranthe MF et al (2014) Cardiac involvement in myotonic dystrophy: a nationwide cohort study. Eur Heart J 35:2158–2164. https://doi.org/10.1093/eurheartj/ehu157

    Article  PubMed  Google Scholar 

  37. Kaminsky P, Brembilla-Perrot B, Pruna L et al (2013) Age, conduction defects and restrictive lung disease independently predict cardiac events and death in myotonic dystrophy. Int J Cardiol 162:172–178. https://doi.org/10.1016/j.ijcard.2011.05.070

    Article  PubMed  Google Scholar 

  38. Priori SG, Blomstrom-Lundqvist C, Mazzanti A et al (2015) 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J 36(41):2793–2867. https://doi.org/10.1093/eurheartj/ehv316

    Article  PubMed  Google Scholar 

  39. Ponikowski P, Voors AA, Anker DS et al (2016) 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 37:2129–2200. https://doi.org/10.1093/eurheartj/ehw128

    Article  Google Scholar 

  40. Kirchhof P, Benussi S, Kotecha D et al (2016) 2016) 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC Endorsed by the European Stroke Organisation (ESO). Eur Heart J 37(38):2893–2962. https://doi.org/10.1093/eurheartj/ehw210

    Article  PubMed  Google Scholar 

  41. Mandrioli J, Ferri L, Fasano A et al (2018) Cardiovascular diseases may play a negative role in the prognosis of amyotrophic lateral sclerosis. Eur J Neurol 25:861–868. https://doi.org/10.1111/ene.13620

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Dr. A.B. Eastwood for advices and english editing of the manuscript and Dr. S. Kaleci for statistical help.

Author information

Authors and Affiliations

  1. Neurology Unit, Department of Biomedical, Metabolic and Neural Sciences, University Hospitals of Modena, Via P. Giardini, 1355, Modena, Italy

    Marco Mazzoli, Alessandra Ariatti & Giuliana Galassi

  2. Pneumology Unit, Santa Maria Bianca Hospital, AUSL Modena, Mirandola, Modena, Italy

    Giancarlo Garuti

  3. Cardiology Unit, University Hospitals of Modena, Via P. Giardini, 1355, Modena, Italy

    Virginia Agnoletto

  4. Respiratory Disease Unit, Department of Medical and Surgical Sciences, University Hospitals of Modena, Via del Pozzo, 71, Modena, Italy

    Riccardo Fantini & Alessandro Marchioni

Authors
  1. Marco Mazzoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alessandra Ariatti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giancarlo Garuti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Virginia Agnoletto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Riccardo Fantini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alessandro Marchioni
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giuliana Galassi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giuliana Galassi.

Ethics declarations

Conflict of interest

The authors have no conflict of interest or sources of funding.

Ethical approval

The authors alone are responsible for the content and writing of the paper.The study was approved by the Ethic Committee AVEN of Modena.

Informed consent

It was obtained from the patients involved in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

a

Marginsplot: the graph shows the marginal prediction of FVC in patients with or without cardiac comorbidities (1 or 0, in the axis), based on a previously fit linear regression model. The band depicts the 95% confidence interval (CI) with the line of best fit. b Receiver Operator Characteristic (ROC) curve for the use of triplet repeat year score in predicting NIV. Area under the curve (AUC= 0.60, p non significant = 0.24)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mazzoli, M., Ariatti, A., Garuti, G. et al. Predictors of respiratory decline in myotonic dystrophy type 1 (DM1): a longitudinal cohort study. Acta Neurol Belg 121, 133–142 (2021). https://doi.org/10.1007/s13760-020-01425-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13760-020-01425-z

Keywords

Search

Navigation